The goal of this research is to investigate the biological function of endogenous bombesin-like peptides in oat cell carcinoma. Bombesin-like peptides are present in the normal lung in low densities; however, in human small (oat) cell lung cancer (SCLC) biopsy tissue and cells in culture the density of immunoreactive bombesin (BN) is elevated by up to three orders of magnitude. In particular, 32 of 34 SCLC cell lines had measurable levels of BN (94%). Of the 32 positive cell lines, BN levels ranged over 180-fold (0.1-18.3 pmol/mg protein). In contrast, immunoreactive BN was not detectable (less than\0.1) in seven non-SCLC lung cancer, one hypernephroma, two melanoma, and three breast cell lines. Therefore, BN-like peptides may serve as unique biochemical markers to monitor the progression of SCLC. These peptides may be stored in the dense core neurosecretory granules present in SCLC cells. When these granules undergo exocytosis, peptides may be secreted into the extracellular fluids. In vitro, immunoreactive BN is secreted from SCLC cell lines into the tissue culture medium by elevating the extracellular K+ or intracellular cAMP concentrations. In vivo, the normal level of immunoreactive BN present in human plasma is 50 fmol/ml. In patients with extensive SCLC, however, the levels may be elevated 40-fold to 2 pmol/ml. Hypersecretion of BN-like peptides from oat cells would likely account for some paraneoplastic syndromes associated with SCLC such as impaired ability to thermoregulate and anorexis. Because BN may function as an important regulatory agent in SCLC, the presence of receptors or BN-like peptides was investigated. In particular, SCLC cell line NCI-H446 had a high density of sites (2000/cell) that bound BN with high affinity (Kd, 0.5 nM). These cell surface receptors, when activated by endogenous BN0-like peptides, may mediate the growth of oat cell carcinoma. (2)